Project Summary Human cytomegalovirus (HCMV) is a ubiquitous b-herpesvirus that can infect individuals throughout the world. Primary infection results in acute low-level mononucleosis like systems followed by a lifelong persistent infection that can involve episodes of reactivation when the immune system is compromised leading to a number of diseases that include hepatitis, retinitis, pneumonitis, vascular sclerosis, as well as severe neurological disorders in neonates. Disease progression is undoubtedly enhanced by the ability of HCMV to infect a broad range of cell types including epithelial cells, endothelial cells, and monocytes. The ability of HCMV to infect these cell types is due to the presence of a glycoprotein complex on the virus envelope known as gH/gL/UL128-131 and evidence suggests that this pentameric protein complex specifically binds cellular receptors on these cell types during entry. However, to date, no receptors have been identified and this represents a major gap in the field. To that end, I have employed a novel cDNA library screen and identified CD147 as the first possible HCMV pentamer-specific receptor. The two specific aims of this project are to characterize the role of CD147 in entry into epithelial cells, endothelial cells, and monocytes as well as identify protein-protein interactions between CD147and the pentameric protein complex.